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Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis

Endometriosis is a disease characterised by the presence of endometrial tissue (the lining of the womb) outside the cavity of the womb. Many women with the disease suffer from menstrual pain and some suffer from infertility. Infertile women with endometriosis are often treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) but have a lower chance of becoming pregnant compared to women who are infertile with blocked tubes. It has been suggested that giving GnRH agonists before IVF or ICSI could increase the chances of pregnancy. We have reviewed the literature and found that treating women for three to six months with GnRH agonists before IVF or ICSI increases the odds of clinical pregnancy four-fold. However, at present there is no information on the effect of this treatment on the incidence of ectopic pregnancy, multiple pregnancies or complications arising for the women or their offspring.

Authors' conclusions:

The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

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Background:

Women with endometriosis who are treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have a lower pregnancy rate compared to women with tubal factor infertility. It has been suggested that the administration of gonadotrophin releasing hormone (GnRH) agonists for a few months prior to IVF or ICSI increases the pregnancy rate.

Objectives:

To determine the effectiveness of administering GnRH agonists for three to six months prior to IVF or ICSI in women with endometriosis.

Search strategy:

We used computer searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register (NRR) and the MDSG Specialised Register of controlled trials. We handsearched proceedings of annual meetings of the American Society for Reproductive Medicine (ASRM) and the European Society for Human Reproduction and Embryology (ESHRE). We reviewed lists of references in original research and review articles. We contacted experts in various countries to identify unpublished trials.

Selection criteria:

We included randomised controlled trials using any GnRH agonist prior to IVF or ICSI to treat women with any degree of endometriosis diagnosed by laparoscopy or laparotomy

Data collection and analysis:

Two independent review authors abstracted data (HNS and JGV). We sent e-mails to investigators to seek additional information. We assessed the validity of each study using the methods suggested in the Cochrane Handbook. The data were checked by the third review author (SD) and any disagreement was resolved by arbitration with the fourth review author (AA). We generated 2 x 2 tables for principal outcome measures. The Peto-modified Mantel-Haenszel technique was used to calculate odds ratios (OR) and assess statistical heterogeneity between studies.

Main results:

Three randomised controlled trials (with 165 women) were included. The live birth rate per woman was significantly higher in women receiving the GnRH agonist compared to the control group (OR 9.19, 95% CI 1.08 to 78.22). However, this was based on one trial reporting "viable pregnancy" only. The clinical pregnancy rate per woman was also significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15). The information on miscarriage rates came from two trials with high heterogeneity and, therefore, results of the meta-analysis were doubtful. The included studies provided insufficient data to investigate the effects of administration of GnRH agonists on multiple or ectopic pregnancies, fetal abnormalities or other complications.